Quantitative Assessment of Radiation-induced Neuroinflammation - A Proof of Principle Study

• Status: Recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

Summary

QARIN 1 is a study of [18F]DPA-714 Translocation Protein (TSPO) Positron Emission Tomography (PET) for longitudinal, quantitative assessment of brain neuroinflammation following whole brain radiation therapy. This TSPO PET, uses a radioactive tracer. An optional MRI (magnetic resonance imaging) will also be performed to monitor brain microstructure damages induced by neuroinflammation.

Primary Objectives

• Assessment of temporal and regional variability of uptake of translocator protein (TSPO) positron emission tomography (PET) tracer.

• Regional variability will be assessed in medial temporal lobe, frontal lobe, and in white matter

• Temporal variability will be assessed by scanning each subject four-times: at baseline (before or within 2 weeks of start of radiation therapy), before start of chemotherapy, at 1 year from the initiation of the radiation therapy, and at 1.5-2 years from the initiation of the radiation therapy

• Correlation of radiation dose in specific brain regions with radiation induced neuroinflammation as measured by uptake of TSPO PET tracer.

Exploratory Objectives

• Assessment of radiation-induced brain microstructure injuries (RIBMI) in specific brain regions (medial temporal lobe, frontal lobe, and in white matter) using advanced magnetic resonance imaging (MRI) techniques.

• Association of radiation dose with MRI measures of RIBMI in these specific brain regions.

• Association of PET measures of RIN with MRI measures of RIBMI.

• Association of PET measure of RIN and MRI measures of RIBMI in specific regions of interest (ROI) with specific domain of neuro-cognition. For example, to investigate whether PET measure of RIN and MRI measures of RIBMI in hippocampal ROI have strongest association with episodic memory; whether frontal lobe cortical ROI are associated with attention and executive function.

• Association of a novel MRI based technique for assessment of RIN with TSPO PET.

• Association of the PET and MRI measure of neuroinflammation within 2- years of completion of radiation with delayed cognitive outcome that will be measured at 3, 4 and 5 years from the completion of radiation

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Jude Children's Research Hospital

Criteria

Inclusion Criteria

• Participant is at least 8 years of age

• Participants with histologically confirmed medulloblastoma and are scheduled to receive 36 Gy craniospinal irradiation

• Participant and/or guardian can understand and is willing to sign a written informed consent document according to institutional guidelines

• Subjects have either have high-affinity or mixed-affinity TSPO binding sites as determined by the single-nucleotide polymorphism (SNP) rs6971 in the TSPO gene.

Exclusion Criteria:

• Participants with a large pseudomeningocele (>4 cm in size) at the surgical site, complications from ventricular access (evidenced by hemorrhage and/or enhancement along the catheter), large subdural effusion in the supra-tentorial compartment (>1 cm in the maximum transverse dimension). All of these are expected to induce inflammation.

• Female participants of childbearing age must not be lactating due to theoretical potential harm to the infant from exposure to radiation.

• Subjects with low-affinity TSPO binding sites as determined by the single-nucleotide polymorphism (SNP) rs6971 in the TSPO gene.

• Pregnant subjects.

• Patients needing sedation for the PET scans.